The present invention relates to a series of new thiazole derivatives, in which the thiazole ring is attached via an unsaturated carbon chain to a rhodanine or thiazolidine-2,4-dione ring system. The invention also provides a process for preparing the compounds as well as methods and compositions for using them.
The enzyme aldose reductase is implicated in many of the complications of diabetes, and inhibitors of its activity can, therefore, be used in the treatment and prevention of such complications. A number of thiazolidine and/or rhodanine derivatives have been found to have the ability to inhibit the activity of aldose reductase. Thus, certain compounds of this type are disclosed in European Patent Publication Nos. 47,109 and 208,040, and in the published Japanese Patent Application Kokai Nos. 56,175/86, 238,286/87 and 179,873/88 (the latter being published after the priority date hereof).
We have now discovered a new series of thiazole derivatives having a very marked ability to inhibit the activity of aldose reductase, which ability is believed to be significantly better than that of the above-mentioned prior art compounds, from which they differ structurally primarily by virtue of the thiazole group. Moreover, these new derivatives include compounds which, upon oral administration, have been found to combine excellent absorption from the gastro-intestinal tract with very low toxicity.